To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Objective: To explore the longitudinal changes and related predictive factors of anxiety and intolerance of uncertainty (IU) among Chinese college students, so as to provide theoretical reference for promoting students mental health. Methods: Intolerance of Uncertainty Scale-short Form and the 7 item Generalized Anxiety Disorder Scale were administered among 5 683 students from 22 universities in Guangdong Province from September 10 to October 17, 2021 (T1, baseline survey), and from March 15 to April 22, 2023 (T2). Using paired sample t-test to analyze the changes in anxiety and IU among college students, a linear regression model was established to explore factors that can predict anxiety, IU and their changes during T1 and T2 periods. Results: During the T1 period, the average scores of anxiety and IU among college students were (3.26±3.46, 34.88±7.96), while during the T2 period, they were (4.41±4.16, 36.40±8.07). During the T2 period, the levels of anxiety and IU among college students were higher than those during the T1 period ( t=19.59, 13.67, P <0.01). The linear regression results showed that age ( B = -0.02 ), moderate ( B =-0.18) and poor ( B =-0.88) mental health status, as well as online browsing of Corona Virus Disease 2019 (COVID-19) epidemic (later called as epidemic) related information for >1-<3 hours ( B =-0.30) and ≥3 hours ( B =-0.22), all of which could negatively predict changes in anxiety during T1 to T2 periods. Living in rural areas ( B =0.11) could positively predict changes in anxiety during T1 to T2 periods ( P <0.05). Moderate ( B =-0.19) and poor ( B =-0.47) mental health status, browsing epidemic related information online for >1-<3 hours ( B =-0.32) and ≥3 hours ( B =-0.33), academic performance being moderately affected by the epidemic ( B =-0.10), and personal planning being moderately affected by the epidemic ( B =-0.13) and severely affected ( B =-0.22), all of which could negatively predict changes in IU during T1 to T2 periods ( P <0.05). Conclusions Levels of anxiety and intolerance of uncertainty increases significantly after epidemic. Mental health status of college students should need long term monitoring, and students with poor mental health should need special attention.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Objective To explore the effect of occupational skills relearning programme on hemiplegic arm motor function and ac-tivities of daily living(ADL)in stroke patients. Methods From February,2022 to August,2023,74 stroke patients in Guangdong Work Injury Rehabilitation Hospital were enrolled and randomly divided into control group(n=37)and experimental group(n=37).The control group received conventional rehabilitation training,and the experimental group received additional occupational skills relearning programme,for three weeks.They were assessed with Fugl-Meyer Assessment-Upper Extremi-ties(FMA-UE),Functional Test for the Hemiplegic Upper Extremity-Hong Kong(FTHUE-HK),Motor Activity Log(MAL)-amount of use(AOU)and MAL-quality of movement(QOM),modified Barthel Index(MBI),and Stroke Impact Scale(SIS)-Hand and SIS-ADL before and after treatment. Results The scores in all assessments improved significantly in both groups(|t|>3.597,P<0.05)after treatment,while the scores of FMA-UE,FTHUE-HK,MAL-AOU,MAL-QOM were higher in the experimental group than in the control group(|t|>2.352,P<0.05). Conclusion Occupational skills relearning programme could promote the recovery of hemiplegic arm motor and activity,and facilitate the use of the hemiplegic arm in daily life in stroke patients.

[Objective]To investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion(MCAO)model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism.[Methods]C57BL/6J mice were randomly divided into Sham operation group(Sham),model group(MCAO),low-dose Zhuangtongyin group(ZTY-L),high-dose Zhuangtongyin group(ZTY-H),with 5 mice in each group.The MCAO group was modelled by silica gel embolization,the middle cerebral artery of mice was embolized for 1h,then the silica gel was pulled out and reperfusion was performed after 72 h;and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted.The neural function of mice was evaluated by Zea-Longa method.TTC staining was used to evaluate the volume of cerebral infarction.The level of brain injury was evaluated by HE staining and Nissl staining.Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain.The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR,and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain.The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR.The expressions of Nrf2,SCL7A11/xCT,Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence.[Results]Zhuangtongyin improved the nerve function of mice after MCAO(P＜0.05)and the cerebral infarction volume of mice(P＜0.05)and alleviate the pathological injury of cerebral cortex cells after MCAO operation.Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO.Additionally,Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA(P＜0.001),a transporter associated with cellular iron ion uptake,in the brains of post-MCAO mice.Furthermore,Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE(P＜0.001)and suppressed ACSL4 mRNA expression in brain tissue post-MCAO(P＜0.001).Besides,Zhuangtongyin downregulated the expression of PTGS2 mRNA(P＜0.001),in the brains of post-MCAO mice.Zhuangtongyin increased the expression of nrf2 into the nucleus(P＜0.001),and increased the expression of xCT and Gpx4 in neurons after MCAO(P＜0.001).[Conclusion]Zhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice,alleviate the pathological damage of cerebral cortex cells,and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway.Therefore,it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective To investigate the effect of facet joint resection at different ranges under endoscopy on the stability of the cervical spine and provide a biomechanical theoretical basis for clinical surgery.Methods A normal finite element model of the cervical spine C5-6 was established based on CT data,and unilateral facetectomy models with different ranges(0,25％,50％,75％,and 100％)of laminectomy were obtained(Models 1-5)by simulating cervical endoscopic surgery.The ranges of motion(ROMs)of C5-6 and the von Mises stresses of the discs for the models in each group were compared and analyzed.Results Except for flexion,Models 1 and 2 showed insignificant changes in ROMs and disc von Mises stresses in each direction compared with those of the normal model.Model 3 showed a noticeable increase in ROMs and disc von Mises stresses in each direction compared with those of the normal model:ROMs under flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation increased by 27％,4％,3％,13％,5％,and 16％,respectively,and von Mises stresses increased by 32％,4％,2％,5％,9％,and 5％,respectively.Models 4 and 5 exhibited a significant increase in the ROMs and disc von Mises stresses in each direction compared to the normal model.For Model 4,ROMs were increased by 27％,14％,6％,24％,7％,167％,and von Mises stresses were increased by 33％,13％,3％,32％,10％,130％.For Model 5,ROMs were increased by 27％,17％,6％,25％,7％,167％,and von Mises stresses were increased by 33％,29％,8％,33％,12％,138％.Conclusions As the range of unilateral facetectomy increased,cervical ROM and disc von Mises stress extremum gradually increased.The cervical spine shows a significant ROM increase and stress changes when facet joint resection on one side exceeds 1/2.More than 1/2 of the facet joint should be preserved during surgery to avoid medical instability.